Learning involves long-lasting changes in the functional properties of neural circuits, and inappropriate activation of these plasticity mechanisms through chronic drug use is thought to underlie drug tolerance and dependence. Understanding how functional changes in individual neurons act within the context of a neural circuit to modify behavior therefore represents a critical challenge in the study of addiction. The goal of the proposed research is to use in vivo calcium imaging to investigate the cellular basis of a simple form of long-term learning, touch habituation, in the nematode C. elegans. We will characterize the normal response and adaptation properties of C. elegans mechanoreceptors by visualizing the activity of touch neurons in response to mechanical stimulation. In addition, by assaying the effect of cloned mechanosensory genes on touch cell activity we will define the molecular requirements for mechanotransduction in these neurons and gain insight into the roles of specific molecules in mechanotransduction. Finally, by simultaneously imaging the activity of multiple neurons in the mechanosensory circuitry, we will gain information about the cellular mechanisms underlying touch habituation. Together, these experiments will address key unanswered questions regarding the molecular mechanisms of mechanosensation and neural plasticity in C. elegans, and are likely to provide insight into analogous processes in vertebrates. These studies will also provide a proving ground for improvements in optical imaging methodologies, which could facilitate the application of this cutting-edge technology to other genetically tractable organisms.